CATECHOLAMINERGIC MECHANISMS OF LATERAL HYPOTHALAMUS - THEIR ROLE IN MEDIATION OF AMPHETAMINE ANOREXIA
CATECHOLAMINERGIC MECHANISMS OF LATERAL HYPOTHALAMUS - THEIR ROLE IN MEDIATION OF AMPHETAMINE ANOREXIA
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DOI：
10.1016/0006-8993(75)90371-6
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发表时间：
1975-01-01
期刊：
影响因子：
2.9
通讯作者：
LEIBOWITZ, SF
中科院分区：
文献类型：
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作者：
LEIBOWITZ, SF
在长期植入脑套管的大鼠中分析了介导苯丙胺对摄食行为抑制作用的脑机制。将药物直接注射到下丘脑前外侧的实验中，发现该区域对安非他明的作用最敏感，产生了以下结果。（1）在6.25纳摩尔（0.8 μg）至400纳摩尔（51.4 μg）的剂量范围内，下丘脑注射的DD-苯丙胺产生了可靠的摄食抑制（6.25纳摩尔时为20%，200纳摩尔时增加至88%），并且发现产生这种效果的效力约为左旋苯丙胺的3倍。（2）局部应用α-甲基酪氨酸（一种多巴胺、去甲肾上腺素和肾上腺素合成的抑制剂）或弗拉-63（一种仅抑制去甲肾上腺素和肾上腺素合成的抑制剂）可完全消除下丘脑注射苯丙胺的兴奋作用。（3）局部应用多巴胺能或β-肾上腺素能受体阻滞剂也能拮抗下丘脑-苯丙胺的这种作用，但不受α-肾上腺素能、肾上腺素能和胆碱能受体阻滞剂的影响。（4）下丘脑外侧区给予低剂量的多巴胺能或β-肾上腺素能受体阻断剂，也能对抗外周注射苯丙胺引起的厌食，这些结果有力地表明，苯丙胺抑制摄食行为的作用可能是通过下丘脑外侧区，可能是通过前区，引起多巴胺和去甲肾上腺素（或者可能是肾上腺素）从外侧下丘脑神经末梢的释放，以及随后刺激位于该区域的多巴胺能和β-肾上腺素能受体。
The brain mechanisms mediating amphetamine's suppressive effect on feeding behavior were analyzed in rats with chronically implanted brain cannulas. Experiments in which drugs were injected directly into the anterolateral hypothalamus, the region found to be most responsive to amphetamine's action, yielded the following results.(1)Over a dose range of 6.25 nmoles (0.8 μg) to 400 nmoles (51.4 μg), hypothalamically injectedd-amphetamine produced a reliable suppression of food consumption (20% at 6.25 nmoles, increasing to 88% at 200 nmoles) and was found to be approximately 3 times as potent asl-amphetamine in yielding this effect.(2)The anorexic effect of hypothalamically injectedd-amphetamine was totally abolished by local administration of α-methyltyrosine, an inhibitor of dopamine, norepinephrine, and perhaps epinephrine synthesis, or by local administration of Fla-63, an inhibitor of only norepinephrine, and perhaps epinephrine, synthesis.(3)This effect of hypothalamicd-amphetamine was also antagonized by locally administered dopaminergic or beta-adrenergic receptor blockers but was unaffected by alpha-adrenergic, serotonergic, and cholinergic blockers.(4)Lateral hypothalamic administration of dopaminergic or beta-adrenergic receptor blockers, at quite low doses, was also effective in antagonizing the anorexia induced byperipherallyadministeredd-amphetamine.These results strongly suggest that amphetamine, in suppressing feeding behavior, acts through the lateral hypothalamus, perhaps the anterior region, causing a release of dopamine and norepinephrine (or perhaps epinephrine) from lateral hypothalamic nerve endings and a subsequent stimulation of dopaminergic and beta-adrenergic receptors located in that region.